The primary safety endpoint in this trial is the standard ocular examination. Toxicity will also be assessed by measurement of vision, hematology and serum chemistries, assays for vector genomes, reported subject history of symptoms and adverse events. [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]

Visual function will be quantified prior to and after vector administration in order to determine whether vector administration affects visual function. [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]

Original Secondary Outcome Measures ICMJE

Not Provided

Current Other Outcome Measures ICMJE

Not Provided

Original Other Outcome Measures ICMJE

Not Provided

Descriptive Information

Brief Title ICMJE

Phase I Trial of Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations

Official Title ICMJE

Phase I Trial of Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus (rAAV2-CBSB-hRPE65) Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations (Clinical Trials of Gene Therapy for Leber Congenital Amaurosis)

Brief Summary

A recombinant adeno-associated virus serotype 2 (rAAV2) vector has been altered to carry the human RPE65 (hRPE65) gene. This vector has been shown to restore vision in animal models that resemble human RPE65-associated Leber congenital amaurosis (LCA), an incurable retinal degeneration that causes severe vision loss. The proposed study is an open label, Phase I clinical trial of subretinal rAAV2-CBSB-hRPE65 administration to individuals with RPE65-associated retinal disease. Five cohorts will be included in this trial. Cohorts 1, 2 and 4 will consist of individuals 18 years of age and older. Cohorts 3 and 5 will consist of individuals between the ages of 8 and 17, inclusive. Enrollment in Cohorts 3 and 5 will begin only after confirming the safety of rAAV2-CBSB-hRPE65 administration in the older groups of participants. This trial will lead to a greater understanding of the safety and thereby potential value of gene transfer in RPE65-associated retinal disease and will have implications for other forms of retinal degenerative disease amenable to this type of intervention.

The goal of this clinical trial is to determine the safety of uniocular subretinal administration of rAAV2-CBSB-hRPE65 in individuals with RPE65-associated retinal disease. Ocular and systemic toxicity will be assessed prior to and following vector administration to determine if there are adverse changes that may be associated with vector administration.

Clinical diagnosis of Leber congenital amaurosis (LCA)/early-onset retinal degeneration (EORD) and of severely impaired visual and retinal function, and best corrected visual acuity of 20/40 or worse in the study eye;

Ability to perform tests of visual and retinal function;

Visible photoreceptor layer on a standard OCT scan;

Good general health;

Ability to comply with research procedures;

Specific for Cohorts 1, 2 and 4: 18 years of age and older;

Specific for Cohorts 3 and 5: Between 8 and 17 years of age, inclusive.